Research Snapshots: Drs. Michael Pace & David Borchelt

Pace RSIn a recent issue of Acta Neuropathologica, Michael Pace, Ph.D., and David Borchelt, Ph.D., professor of neuroscience, and collaborators explored the presence of misfolded proteins in neurodegenerative disease.

The accumulation of misfolded proteins is a uniquely common feature of many neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Lou Gehrig’s disease and frontotemporal dementia. Normally, one or two proteins will “define” each disease. For example, a diagnosis with Alzheimer’s disease is dependent upon the presence of two misfolded proteins called tau and amyloid-β. However, we have recently demonstrated that hundreds of proteins appear to misfold aside from those that are classically associated with neurodegeneration.

In mice that exhibit disease-relevant tau pathology, the number of misfolded proteins increases with age (a) and the amount of tau (b). There was an overlap of misfolded protein content with a different mouse that has disease-relevant amyloid-β (d). Overall, our results demonstrate that additional proteins misfold in the presence of neurodegenerative disease pathologies which could act as an irritant to cellular fitness.

View the published manuscript in Acta Neuropathologica.